Arabinogalactan for enhancing the adaptive immune response

ABSTRACT

The present invention discloses a composition containing Arabinogalactan for enhancing the adaptive immune response in subjects to foreign antigen(s) by administering said composition prior, during and after the phase of exposure to said foreign antigen(s). Furthermore, the present invention relates to a vaccination kit comprising a composition comprising Arabinogalactan and a vaccine.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims the benefit of priority from U.S. ProvisionalPatent Application No. 61/247,204 filed Sep. 30, 2009, the disclosure ofwhich is incorporated herein by reference.

The subject of the present invention is a composition containingArabinogalactan for enhancing the adaptive immune response in subjectsby administering said composition prior, during and after the phase ofexposure to a foreign antigen. Furthermore, the present inventionrelates to a vaccination kit comprising a composition containingArabinogalactan and a vaccine.

BACKGROUND OF THE INVENTION

The immune system is a highly complex orchestration of severalsub-systems which protect the host against infectious agents andcancerous cells. The immune system performs surveillance and mustappropriately attack pathogens; it must also be able to recognize andspare cells which belong to the host. Immunomodulation is the ability ofthe hormones and other molecules to selectively alter the sensitivity ofthe immune system to mount attacks in response to antigenic stimulation.This is preferred to overstimulation (or hypersensitivity) of the immunesystem which may lead to damage to the host cells. The immune systemconsists of two major parts, namely the innate arm and the adaptive arm.

Said adaptive arm rests on the intricate interplay of various types ofimmune cells like dendritic cells, T-cells and B-cells as well as a widerange of immunomodulatory substances like cytokines to mount asuccessful production of antibodies. However, if the immune systemencounters a foreign antigen for the first time, its reaction isfrequently too slow/too weak to stop the initial spread of said antigen.Thus, there is a need to keep the immune system in a “primed” orheightened state of alert prior to the first encounter of a foreignantigen.

Furthermore, there is a need to enhance an on-going immune response inorder to have the immune system clear the foreign antigen from the bodyas quickly as possible.

In order to help the immune system ward off potentially harmfulinvaders, a method of artificial induction of an immune response called“vaccination” was systematically employed for the first time in the18^(th) century. Vaccination is the administration of antigenic material(the vaccine) to produce immunity to a disease. Vaccines can prevent orameliorate the effects of infection by a pathogen. Vaccination isgenerally considered to be the most effective and cost-effective methodof preventing infectious diseases. The material administered can eitherbe live but weakened forms of pathogens (bacteria or viruses), killed orinactivated forms of these pathogens, or purified material such asproteins.

However, a vaccination with the antigenic material alone frequentlyfails to provoke an immune response that is sufficiently strong toconvey complete or even partial immunity. Thus, adjuvants are used toboost the immune response. Broadly speaking, adjuvants fall into twoclasses: inorganic and organic adjuvants.

Typical examples of inorganic adjuvants are aluminium salts, e.g.aluminium phosphate and aluminium hydroxide. Due to their low tonon-existent toxicity, they are the most widely used adjuvants in humanvaccinations.

Organic adjuvants are usually selected from components of the bacterialcell wall like lipopolysaccharide (LPS) and from endocytosed nucleicacids such as double-stranded RNA (dsRNA), single-stranded DNA (ssDNA),and unmethylated CpG dinucleotide-containing DNA. The reason for this isthat immune systems have evolved to recognize and react against thesespecific antigenic moieties.

Thus, there is a need for additional adjuvants that help boost an immuneresponse while at the same time being non-toxic and that do not induceany severe side effects in subjects.

Larch Arabinogalactan is a highly branched polysaccharide that iscomposed of galactose units and arabinose units in the approximate ratioof 6:1. It is a fine, dry, light brown powder with neutral taste and, incase it is extracted from larch trees, a mild pine-like odour. Itdissolves quickly in water or juice.

Studies on improvement of response to a pneumococcal vaccine by adultsinclude revaccination, the addition on conjugates to the vaccine andalternative antigenic substances.[1] Experiments have also beenconducted on the use of supplements, including zinc, vitamin A andL-arginine to increase the response to the vaccine.[2,3] Some plants areknown to contain substances that modulate the immune system. As anexample, an extract of the plant Uncana tomentosa was reported toenhance the response to a pneumococcal vaccine in male volunteers,elevating lymphocyte/neutrophil ratios and increasing the persistence ofthe antibody response to the vaccine.[4]

Several immune-enhancing herbs, including Echinacea purpurea, Baptistatinctoria, Thuja occidentalis, Angelica acutiloba, and Curucuma longaand the medicinal mushroom Ganoderma lucidum contain compounds known asArabinogalactans.[5] Larch arabinogalactan has demonstratedimmunomodulating activity in vitro and in vivo.[6,7]. However, saidimmunomodulating effect was thus far limited to the innate arm of theimmune system. Nothing in the state of the art indicates that LarchArabinogalactan is capable of modulating the adaptive arm of the immunesystem.

DISCLOSURE OF THE INVENTION

The technical problems laid out above are surprisingly solved by using acomposition containing Arabinogalactan for enhancing the adaptive immuneresponse in subjects as defined in the claims.

Specifically, the present invention discloses a composition containingArabinogalactan for enhancing the adaptive immune response againstforeign antigen(s), whereby said composition is administered to thesubjects prior, during and after the phase of exposure to saidantigen(s).

“Subjects” according to the invention are vertebrates, preferablymammals and birds, more preferably swine, poultry, beef cattle, dogs,cats, goats and horses, most preferably humans.

“Antigen” according to the invention relates to any substance capable ofbeing recognized by the adaptive arm of the immune system. Preferably,the antigen is either an exogenous or endogenous antigen, whileautoantigens are excluded. Preferably, the antigen according to theinvention is derived from a pathogen, preferably a virus or a bacterium.

A “virus” according to the invention is a member of one of the fiveorders as defined by the ICTV classification, i.e. Caudovirales,Herpesvirales, Mononegavirales, Ndovirales, and Picomavirales or amember of one of the seven Groups of the Baltimore classification, i.e.dsDNA viruses, ssDNA viruses, dsRNA viruses, (+)ssRNA viruses, (−)ssRNAviruses, ssRNA-RT viruses, dsRNA-RT viruses. Preferably, the virusaccording to the invention is a member of the family ofOrthomyxoviridae, more preferably a member of the genera InfluenzavirusA-C, even more preferably of the species Influenza A, Influenza B orInfluenza C virus and most preferably of the serotype H1N1, H1N2, H2N2,H3N1, H3N2, H3N8, H5N1, H5N2, H5N3, H5N8, H5N9, H7N1, H7N2, H7N3, H7N4,H7N7, H9N2 or H10N7.

A “bacterium” according to the invention generally refers to aprokaryotic member of the domain Bacteriae. More preferably, a bacteriumaccording to the invention belongs to one of the currently known phyla,i.e. Actinobacteria, Aquificae, Bacteriodetes/Chlorobi,Chlamydiae/Verrucomicrobia, Chloroflexi, Chrysiogenetes, Cyanobacteria,Deferribacteres, Deinococcus-Thermus, Dictyoglomi,Fibrobacteres/Acidobacteria, Firmicutes, Fusobacteria, Gemmatimonadetes,Nitrospirae, Planctomycetes, Proteobacteria, Spirochaetes,Synergistetes, Tenericutes, Thermodesuflobacteria and Thermotogae.

Even more preferably, the bacterium according to the invention belongsto the genus Streptococcus, Staphylococcus, Chlamydia, Mycobacterium,Clostridium, Salmonella, Haemophilus, Legionella, Campylobacter,Bacillus, Escherichia, Enterococcus, Klebsiella, Lactobacillus orPseudomonas.

Most preferably, the bacterium according to the invention is the strainStreptococcus pneumoniae.

Other antigens according to the invention include toxins, prions,viroids and satellites.

“Arabinogalactan” according to the invention is to be understood asrelating to any compound that is composed of galactose units andarabinose units in the approximate ratio of 100:1 to 1:1, preferably6:1, Specifically, Arabinogalactan according to the invention ispreferably characterized by having a backbone of (1→3)-linkedβ-D-galactopyranosyl units, each of which bears a substituent at the C-6position. Most of these side chains are galactobiosyl units containing a(1→6)-β-D-linkage as well as α-L-arabinofuranosyl units. However, thescope of the present invention also encompasses Arabinogalactanderivatives, e.g. where Arabinogalactan is in covalent association withvarying amounts of protein (Arabinogalactan-proteins (AGPs) as describedin Classen et al., “Characterization of an Arabinogalactan-proteinisolated from pressed juice of Echinacea purpurea by precipitation withthe β-glucosyl Yariv reagent”, Carbohydrate Research, 327 (2000),497-504). Other derivatives include quaternized or lipidated forms ofArabinogalactan.

According to the invention, it may be preferred that the Arabinogalactanis derived from plants, namely dicotyledons and monocotyledons, withdicotyledons being preferred. It may further be preferred that theArabinogalactan according to the invention is derived from pinophyta,more preferably pinaceae. It may be most preferred that theArabinogalactan according to the invention is derived from Larch trees(Larix spp.), especially Larix laricina. “Composition” according to theinvention relates to any composition that includes Arabinogalactan asdefined above in an amount of 0.5 mg-30 g, preferably in an amount of0.5 g-15 g and most preferably in an amount of 1.0-4.5 g.

Preferably, the composition containing Arabinogalactan is administered70 days before the phase of exposure to foreign antigen(s), morepreferably 50 days and most preferably 30 days.

It may be preferred that the composition containing Arabinogalactan isadministered until 92 days, more preferably until 72 days and mostpreferably until 42 days after the phase of exposure to foreignantigen(s).

The composition containing Arabinogalactan may be administered in liquidor solid form. Preferably the Arabinogalactan is administered in theform of functional beverages, functional foods such as bars, breakfastcereals etc or as dietary supplements such as capsules, tablets, drypowder blends or premixes.

Preferably, the composition containing Arabinogalactan is administeredto the subject on a daily basis. However, it may also be preferred thatthe composition containing Arabinogalactan is administered in longer orshorter intervals.

Generally, the composition containing Arabinogalactan may be used inconjunction with any vaccine. However, it may be preferred that thevaccine according to the invention is directed against an antigenderived from or being part of an agent selected from the groupconsisting of bacteria, viruses, toxins, prions, viroids and satellites.Said agent may also be used as a whole in the vaccination in either liveor inactivated form.

It may be preferred that the vaccine is a pneumococcal vaccine. It mayfurther be preferred that the vaccine is directed against bacteria fromthe genus Streptococcus, Staphylococcus, Chlamydia, Mycobacterium,Clostridium, Salmonella, Haemophilus, Legionella, Campylobacter orPseudomonas., especially the strain Streptococcus pneumoniae.

The vaccination procedure can be carried out using any methodology knownin the state of the art. Specifically, said vaccination procedure may becarried out subcutaneously, intramuscular, orally, nasally, byinhalation or via patches.

It may also be preferred that the vaccination procedure is carried outrepeatedly to enhance the immune response.

Another aspect of the present invention concerns a kit comprising avaccine and a composition containing Arabinogalactan. Said kit may beused to enhance the adaptive immune response upon vaccination.

The invention will be further described in the following, non-limitingexamples.

EXAMPLES Example 1 Investigational Products

The Resistaid™ product contains arabinogalactan extracted from Larchtrees (Larix spp., mostly Larix laricina). Arabinogalactan is a highlybranched polysaccharide that is composed of galactose units andarabinose units in the approximate ratio of 6:1. Resistaid™ is a fine,dry, light brown powder with neutral taste and a mild pine-like odor. Itdissolves quickly in water or juice. Resistaid™ is produced via a waterextraction patented process (U.S. Pat. No. 5,756,098; EP 86608). TheLarch arabinogalactan used in the Resistaid™ product has been AffirmedGRAS by the FDA (GRN000084).

The placebo was maltodextrin (Maltin M100). The test product and theplacebo were administered by mixing the powders into a beverage of thesubject's choice for a maximum period of 72 days. The subjects wereadvised to take their dosage (4.5 g) once a day in the morning withbreakfast. First intake of the study medication was on Day 1.

Subjects

Subjects between the ages of 18 and 65 were recruited for the study inthe usual manner (subject database and community advertisements).Subjects were phone-screened prior to scheduling a screening visit.

Subjects were included if they were 18-65 years of age, had a Body MassIndex (BMI)>18 kg/m2 and <30 kg/m2 at screening, agreed to all studyvisits and visit procedures, agreed to use approved forms of birthcontrol, and agreed not to initiate/change any exercise or diet programsduring the study. Subjects were excluded if they had previously had thepneumococcal vaccine, had allergies to the test product, had any majorsystemic, inflammatory or chronic disease, had any active infection orinfection in the past month requiring antibiotics or anti-viralmedication, used immunosuppressive drugs in the prior 5 years, wereknown to have alcohol or drug abuse, were pregnant or lactating or hadany medical condition which in the opinion of the investigator mightinterfere with the subject's participation in the trial.

Study Design

The study was a randomized, double-blind, placebo-controlled, parallelgroup trial with an active investigational period of 72 days. Theprimary objective was to assess the immunomodulatory effect ofResistaid™ on selective markers of immune function in the face ofantigenic challenge by the pneumococcal pneumonia vaccine. The primaryendpoints included 7 different pneumococcal IgG antibodies. Thesecondary objective was determine whether the Resistaid™ product wouldstimulate other arms of the immune system to which there was no directantigenic stimulus. Secondary endpoints included salivary IgA, whiteblood cell counts, complement (C3 and C4) and inflammatory cytokinelevels. The study was conducted at the Medicus Research clinicalresearch site located in Northridge, Calif. IRB approval was obtainedprior to the initiation of any study activities (Copernicus Group IRB,Cary, N.C.).

Subjects meeting the inclusion/exclusion criteria for this study wereassigned to group using randomized block design. Double-blinding wasensured by identical sachets, outer package, labelling, color, andconsistency of both investigational products (investigational studyproduct and placebo). Unblinding of the entire research team, includingdata analysis team did not occur until after the analysis was completed;subjects were blinded throughout the trial.

The subjects in the study came to the research clinic for a total of 5visits (V1-V5) over 72 days. Subjects took the first dose of assignedstudy product at the screening visit (V1-Day 0) and continued to takethem over the entire study. They received the 23-valent pneumococcalvaccine at the baseline visit which took place 30 days after they begantaking the product or placebo (V2-Day 30). They came in for safetymonitoring the day immediately following the vaccine (V3-Day 31) toobserve the reaction at the vaccine administration site. Then subjectsreturned 21 days after vaccine (V4-Day 51) and finally 42 days aftervaccine administration (V5-Day 72). On study visits, blood, urine andsaliva were collected and subjects were queried regarding any change inhealth status. Additionally, they were assessed for compliance byinterview, diary, and through assessment of returned study productbottles.

The most potentially immunogenic pneumococcal antibodies (Ab) weredetermined in consultation the UCLA Vaccine Center as the antibodiesmost likely to respond to vaccination with the commercially available23-valent pneumococcal vaccine. These antibodies included 4, 6B, 9V, 14,18C, 19F, and 23F. Salivary IgA was measured to monitor for non-specificeffects on the adaptive immune system.

Other markers of immune function were chosen to represent the innate armof the immune system including white blood cell counts (totals andsubtypes), inflammatory cytokines, and complement (C3 and C4). Safetymonitoring included: body temperature, blood pressure, heart rate,physical exam, urinalysis, complete blood counts (CBC) and acomprehensive metabolic panel (CMP) including kidney and liver functiontests.

Analyses

Excel 2003 (Microsoft Corp, Redmond Wash.), was used for data entry,validation, restructuring, calculating changes in variables over time,reorganizing and reformatting results, and preparing graphs. Statisticalanalyses were performed using SPSS Base System ver. 17 (SPSS Inc.,Chicago Ill.).

Data was analyzed using paired sample t-tests for within subject meanscomparisons, independent sample t-tests for between group comparisons(Placebo vs. the active groups individually). Difference scores for bothwithin and between group comparisons (Placebo vs. the active groupsindividually) were analyzed using appropriate t-tests. Analysis wascompleted before the blinding code was broken.

Results Subjects

Sixty five (65) subjects were screened in person at the research clinicand 53 qualified for randomization at the screening visit (V1). Of the53, 8 did not return for V2 and therefore a total of 45 subjects wereincluded in the intent-to-treat analysis. The subject baselinecharacteristics are given in Table 1. There were no significantdifferences between groups at baseline and there were no significantchanges in body weight during the study in either group.

TABLE 1 Subject Demographics Resistaid(TM) Placebo N 21 24 Male 6(42.9%) 16 (66.7%) Female 12 (57.1%) 8 (33.3%) Age (range) 33.52 (19-62)38.25 (20-64)

Pneumococcal IgG Antibodies

Pneumococcal IgG antibody subtypes 4, 6B, 9V, 14, 18C, 19F, and 23F weremeasured on Days 0 (V1), 51 (V4), and 72 (V5). There were no significantdifferences between the groups at baseline (Day 0).

Pneumococcal IgG levels increased from baseline as expected in responseto the vaccine. Supplementation with Resistaid™ caused a significantlygreater increase from baseline in pneumococcal IgG antibody subtypes 18Cand 23F at both 51 and 72 days (Table 2). Mean values between groupswere also significantly greater in the Resistaid group for both days 51and 72 for these two subtypes (Table 3).

Change scores from baseline and mean values were greater in theResistaid group than placebo for most timepoints in Ab subtypes 4, 6B,9V, and 19F, but these differences did not reach statisticalsignificance.

TABLE 2 Comparisons in mean values for Pneumococcal Subtypes 18C and 23F18C Abs Day 0 Resistaid 21 1.4905 2.97891 .65005 .061 (Screen) Placebo24 .7167 1.34993 .27555 Day 51 Resistaid 21 9.5667 7.96438 1.73797 .006Placebo 24 5.0583 5.80157 1.18424 Day 72 Resistaid 21 9.1048 7.531961.64361 .008 Placebo 24 4.9333 5.26338 1.07438 23F Abs Day 0 Resistaid21 .7429 .92605 .20208 .059 (Screen) Placebo 24 1.0833 1.87516 .38277Day 51 Resistaid 21 7.0714 7.40602 1.61613 .002 Placebo 24 4.32504.62011 .94308 Day 72 Resistaid 21 7.0238 7.31505 1.59627 .041 Placebo24 4.5458 5.23084 1.06774

TABLE 3 Comparisons in change from baseline values for PneumococcalSubtypes 18C and 23F 18c Day 51 to Day 0 Resistaid 21 8.0762 7.124811.55476 .033 (Screen) Change Placebo 24 4.3417 5.09645 1.04031 Day 72 toDay 0 Resistaid 21 7.6143 6.80605 1.48520 .012 (Screen) Change Placebo24 4.2167 4.63270 .95789 23F Day 51 to Day 0 Resistaid 21 6.3286 7.36180160643 .001 (Screen) Change Placebo 24 3.2417 4.28251 .87416 Day 72 toDay 0 Resistaid 21 6.2810 7.16782 1.56415 .003 (Screen) Change Placebo24 3.4625 4.23985 .86546

Salivary IgA

There were no significant changes increases in salivary IgA from Day 0to Days 51 or Day 0 to Day 72 in either group. There were also nosignificant differences in the mean values between groups.

White Blood Cells

Comparisons between the Arabinogalactan and Placebo groups on Days 0,30, 31, 51 or 72 found no significant differences in white blood cellcounts. The change from baseline Day 0 to Day 72 was significantlygreater in the Arabinogalactan group than the Placebo group (p=0.045),however the magnitude of the change scores were too small to beclinically significant.

There were no significant differences in lymphocyte, neutrophil,monocyte, or basophil counts when comparing mean values between groupsat any timepoint. When comparing change from baseline at each timepoint,there were no difference between groups for lymphocytes, neutrophils, ormonocytes. Change from baseline comparisons for basophils were notdifferent except for the change from Day 0 to Day 72 in which there wasa small but significant difference in favor of the placebo group(p=0.042).

Eosinophil counts were different between groups at Day 30 (p=0.006) andDay 51 (p=0.014) in favor of the Arabinogalactan group. The change frombaseline to Day 31 and the change from baseline to Day 51 were alsosignificant in favor of the Arabinogalactan group (p=0.035 and p=0.006respectively).

Complement

Comparisons of means and changes from baseline for complement levelsbetween the Arabinogalactan and Placebo groups were not significantlydifferent.

Cytokines

Analysis of inflammatory cytokine levels was performed using sandwichimmunoassay (Affymetrix, San Diego, Calif.). Comparison of cytokinelevels between groups found no significant differences in means forepithelial neutrophil-activating peptide (ENA)-78, eotaxin, granulocytemonocyte colony stimulating factor (GM-CSF), interferon-gamma (IFNg),interleukin (IL)-10, IL-12P40, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-8,monocyte chemotactic protein (MCP)-1, MCP-3, platelet-derived growthfactor (PDGF)-BB or tumor necrosis factor (TNF)-alpha. When comparingthe cytokine change from baseline values between groups, only the IL-6change from Day 0 to Day 31 showed a significant difference in favor ofthe Arabinogalactan group (p=0.046).

Safety

No serious adverse events were reported during this study. There werenine mild to moderate adverse events: two in the Arabinogalactan groupand seven in the Placebo group. The adverse events were determined to beunrelated to study product and were exacerbations of pre-existingmedical conditions. All AE's were followed by the medical staff at theresearch clinic.

LITERATURE

-   1. Artz A S, Ershler W B, Longo D L: Pneumococcal vaccination and    revaccination of older adults. Clin Microbiol Rev 2003, 16: 308-318.-   2. Deloria-Knoll M, Steinhoff M, Semba R D, Nelson K, Vlahov D,    Meinert C L: Effect of zinc and vitamin A supplementation on    antibody responses to a pneumococcal conjugate vaccine in    HIV-positive injection drug users: a randomized trial. Vaccine 2006,    24: 1670-1679.-   3. Moriguti J C, Ferriolli E, Donadi E A, Marchini J S: Effects of    arginine supplementation on the humoral and innate immune response    of older people. Eur J Clin Nutr 2005, 59: 1362-1366.-   4. Lamm S, Sheng Y, Pero R W: Persistent response to pneumococcal    vaccine in individuals supplemented with a novel water soluble    extract of Uncaria tomentosa, C-Med-100. Phytomedicine 2001, 8:    267-274.-   5. Roxas M, Jurenka J: Colds and influenza: a review of diagnosis    and conventional, botanical, and nutritional considerations. Altern    Med Rev 2007, 12: 25-48.-   6. Kelly GS: Larch arabinogalactan: clinical relevance of a novel    immune-enhancing polysaccharide. Altern Med Rev 1999, 4: 96-103.-   7. Currier N L, Lejtenyi D, Miller S C: Effect over time of in-vivo    administration of the polysaccharide arabinogalactan on immune and    hemopoietic cell lineages in murine spleen and bone marrow.    Phytomedicine 2003, 10: 145-153.

1. A composition containing Arabinogalactan for enhancing the adaptiveimmune response against foreign antigen(s), whereby said composition isadministered to the subjects prior, during and after the phase ofexposure to said foreign antigen(s).
 2. Composition according to claim1, whereby the administration starts 70 days before the phase ofexposure to said foreign antigen(s), more preferably 50 days and mostpreferably 30 days.
 3. Composition according to claim 1, whereby theadministration takes place until 92 days, more preferably until 72 daysand most preferably until 42 days after the phase of exposure to saidforeign antigen(s).
 4. Composition according to claim 1, whereby saidcomposition is administered in liquid or solid form, preferably in theform of functional beverages, functional foods such as bars, breakfastcereals etc. or as dietary supplements such as capsules, tablets, drypowder blends or premixes.
 5. Composition according to claim 1, wherebysaid composition is administered on a daily basis.
 6. Compositionaccording to claim 1, whereby said composition is administered in anamount of 0.5 mg-30 g per each individual round of administration, morepreferably in an amount of 0.5 g-15 g and most preferably in an amountof 1.0 g-4.5 g.
 7. Composition according to claim 1, whereby theexposure to foreign antigen(s) is effected by vaccination. 8.Composition according to claim 1, whereby the vaccine used in thevaccination phase is directed against an antigen derived from or beingpart of an agent selected from the group consisting of bacteria,viruses, toxins, prions, viroids and satellites.
 9. Compositionaccording to claim 8, whereby said agent is used as a whole in thevaccination.
 10. Composition according to claim 9, whereby said agent isused in a live or inactivated form.
 11. Composition according to claim1, whereby said vaccine is a pneumococcal vaccine.
 12. Compositionaccording to claim 11, whereby said pneumococcal vaccine is directedagainst bacteria from the genus Streptococcus, preferably the strainStreptococcus pneumoniae.
 13. Composition according to claim 1, wherebysaid vaccination is carried out subcutaneously, intramuscular, orally,nasally, by inhalation or via patches.
 14. Composition according toclaim 1, whereby the vaccination is carried out repeatedly, preferablyonce every 6 months, more preferably once a year and most preferablyonce every 10 years.
 15. Kit comprising a composition containingArabinogalactan and a vaccine.
 16. The kit according to claim 15,whereby said vaccine is a pneumococcal vaccine, preferably a vaccinedirected against bacteria from the genus Streptococcus, more preferablythe strain Streptococcus pneumoniae.